Palbociclib + Chemotherapy for Childhood Leukemia and Lymphoma

No longer recruiting at 19 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 drugs

Disqualifiers: Pregnancy, Infections, Genetic syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 32 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for children and teens with relapsed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL). Researchers are evaluating the effectiveness of palbociclib, a cancer drug, alongside standard chemotherapy. The goal is to determine if this combination can benefit children whose cancer has returned after treatment. This trial may suit those who have previously experienced a relapse of ALL or LL and face ongoing challenges from these conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking certain medications before starting. You cannot take other anti-cancer agents, except hydroxyurea, which can be continued until 24 hours before the trial starts. Also, you must avoid drugs that strongly affect the liver enzyme CYP3A4 for 14 days before and during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining palbociclib with chemotherapy is safe and well-tolerated in children and young adults with relapsed Acute Lymphoblastic Leukemia (ALL) and lymphoblastic lymphoma (LL). Studies found that this combination did not cause severe side effects that would halt treatment. Patients managed the suggested dose of 50 mg/m²/day for 21 days well. Although this study is in its early stages, earlier research has shown promise without causing major problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about Palbociclib for childhood leukemia and lymphoma because it targets cancer cells in a novel way. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, Palbociclib specifically inhibits enzymes called cyclin-dependent kinases (CDKs), which are crucial for cancer cell division. This targeted approach has the potential to reduce side effects while enhancing treatment effectiveness. Additionally, combining Palbociclib with standard chemotherapy could improve outcomes by attacking the cancer from multiple angles, offering new hope for patients with these challenging conditions.

What evidence suggests that this treatment might be an effective treatment for childhood leukemia and lymphoma?

Research has shown that palbociclib, one of the treatments in this trial, may help treat relapsed childhood Acute Lymphoblastic Leukemia (ALL) and lymphoblastic lymphoma (LL) when combined with chemotherapy. Studies have found that palbociclib can be safely combined with chemotherapy, leading to complete recovery in some patients. Early research suggests that palbociclib may effectively stop cancer cell growth. While treatments for childhood leukemia have improved, palbociclib offers a new option for those whose cancer has returned. This combination treatment aims to improve recovery chances for children with relapsed leukemia and lymphoma. ^{2 6 7 8 9}

Who Is on the Research Team?

Elizabeth Raetz, MD

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children with relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL). They should have a certain level of bone marrow blasts, measurable disease, and be in good enough health to participate. Patients must not have been treated with palbociclib before and should meet specific heart, kidney, and liver function requirements.

Inclusion Criteria

I am mostly able to care for myself, regardless of my age.

My leukemia has relapsed at least once for T-lineage and twice for B-lineage.

I have never taken palbociclib or similar medications.

Exclusion Criteria

You are currently taking part in another study that involves testing an experimental drug.

I am not taking medication that strongly affects certain liver enzymes.

I do not have any infections that are currently uncontrolled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Palbociclib in combination with chemotherapy for one cycle, 32 days

32 days

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for adverse events and response to treatment

Up to 26 months

What Are the Treatments Tested in This Trial?

Interventions

• Palbociclib

Trial Overview The study tests the drug palbociclib combined with standard chemotherapy in pediatric patients who've had ALL or LL return after treatment. Palbociclib will be given at a starting dose of 50 mg/m^2/day for 21 days alongside re-induction chemotherapy.

How Is the Trial Designed?

Group I: Treatment (Palbociclib) Experimental Treatment 9 Interventions

Patients receive Palbociclib 50 mg/m\^2 (starting dose with maximum dose of 100 mg) PO (or via NG-tube) once daily on Days 1-21; Intrathecal cytarabine (IT ARAC) age-based dosing on Day 1, Doxorubicin 60 mg/m\^2 IV push or infusion over 1-15 min on Day 4; Prednisone or prednisolone 40 mg/m\^2 PO divided BID or TID on days 4-31; Vincristine 1.5 mg/m\^2 (maximum dose 2 mg) IV push or mini-bag per institutional policy on days 4, 11, 18, and 25; and Pegaspargase 2500 IU/m\^2 IV over 1-2 hours on Days 5, and 18. If CNS3 leukemia is present, patients receive Intrathecal Triple Therapy (ITT) age-based dosing on days 4, 11, 18, and 25. Patients known to be CNS3 at study entry may receive ITT on Day 1 rather than IT ARAC. If CNS1 and 2 leukemia present, patient receive Methotrexate (IT MTX) age-based dosing on Days 18 and 32. Treatment will be given for one cycle, 32 days, in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37553297/

A Children's Oncology Group study (AINV18P1) - PubMed - NIH Conclusions: Palbociclib in combination with re-induction chemotherapy was well tolerated with a RP2D of 50 mg/m2 /day for 21 days. Complete responses were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03792256

Study Details | NCT03792256 | Palbociclib in Combination ... AINV18P1 is a Phase 1 study where palbociclib will be administrated in combination with a standard re-induction platform in pediatric relapsed Acute ...

3. researchgate.net researchgate.net/publication/372993103_Palbociclib_in_combination_with_chemotherapy_in_pediatric_and_young_adult_patients_with_relapsedrefractory_acute_lymphoblastic_leukemia_and_lymphoma_A_Children's_Oncology_Group_study_AINV18P1

Palbociclib in combination with chemotherapy in pediatric ... While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212623000607

A phase I study of the combination of palbociclib and ... Preclinical studies suggest that the combination of the CDK4/6 inhibitor palbociclib and dexamethasone may be effective in targeting leukemic cell growth.

5. haematologica.org haematologica.org/article/view/11894

Relapsed childhood T-cell acute lymphoblastic leukemia ... Impressive results were seen in the 20 pediatric and adult patients with relapsed T-ALL who received this CAR-T, with 85% CR and 95% ORR by day ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118702528

Safety of Palbociclib in Combination with Chemotherapy ... Palbociclib in combination with 4-drug re-induction chemotherapy is safe and well tolerated in children and young adults with relapsed/refractory ALL and LLy.

7. fda.gov fda.gov/media/188805/download?attachment

Ibrance (palbociclib) Written Request Study 1: An open-label, dose-escalation and cohort expansion study to evaluate the safety, pharmacokinetics (PK) and antitumor activity of palbociclib in ...

8. researchgate.net researchgate.net/publication/346664480_Safety_of_Palbociclib_in_Combination_with_Chemotherapy_in_Pediatric_and_Young_Adult_Patients_with_RelapsedRefractory_Acute_Lymphoblastic_Leukemia_and_Lymphoma_A_Children's_Oncology_Group_Pilot_Study

A Children's Oncology Group Pilot Study | Request PDF Conclusions: Palbociclib in combination with 4-drug re-induction chemotherapy is safe and well tolerated in children and young adults with ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pbc.30609

Palbociclib in combination with chemotherapy in pediatric ... Palbociclib in combination with re-induction chemotherapy was well tolerated with a RP2D of 50 mg/m 2 /day for 21 days. Complete responses were observed among ...